{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T14:27:36Z","timestamp":1770215256784,"version":"3.49.0"},"reference-count":19,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2005,8,8]],"date-time":"2005-08-08T00:00:00Z","timestamp":1123459200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2005,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Since our original demonstration of the metabolism of 1\u03b1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub> into 1\u03b1,25(OH)<jats:sub>2<\/jats:sub>\u20103\u2010epi\u2010D<jats:sub>3<\/jats:sub> in human keratinocytes, there have been several reports indicating that epimerization of the 3 hydroxyl group of vitamin D compounds is a common metabolic process. Recent studies reported the metabolism of 25OHD<jats:sub>3<\/jats:sub> and 24(<jats:italic>R<\/jats:italic>),25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub> into their respective C\u20103 epimers, indicating that the presence of 1\u03b1 hydroxyl group is not necessary for the 3\u2010epimerization of vitamin D compounds. To determine whether the presence of a 25 hydroxyl group is required for 3\u2010epimerization of vitamin D compounds, we investigated the metabolism of 1\u03b1OHD<jats:sub>3<\/jats:sub>, a non\u201025 hydroxylated vitamin D compound, in rat osteosarcoma cells (ROS 17\/2.8). We noted metabolism of 1\u03b1OHD<jats:sub>3<\/jats:sub> into a less polar metabolite which was unequivocally identified as 1\u03b1OH\u20103\u2010epi\u2010D<jats:sub>3<\/jats:sub> using the techniques of HPLC, GC\/MS, and <jats:sup>1<\/jats:sup>H\u2010NMR analysis. We also identified 1\u03b1OH\u20103\u2010epi\u2010D<jats:sub>3<\/jats:sub> as a circulating metabolite in rats treated with pharmacological concentrations of 1\u03b1OHD<jats:sub>3<\/jats:sub>. Thus, these results indicated that the presence of a 25 hydroxyl group is not required for 3\u2010epimerization of vitamin D compounds. Furthermore, the results from the same studies also provided evidence to indicate that 1\u03b1OH\u20103\u2010epi\u2010D<jats:sub>3<\/jats:sub>, like 1\u03b1OHD<jats:sub>3<\/jats:sub>, is hydroxylated at C\u201025. We then evaluated the biological activities of 1\u03b1OH\u20103\u2010epi\u2010D<jats:sub>3.<\/jats:sub> Treatment of normal rats every other day for 7 days with 2.5 nmol\/kg of 1\u03b1OH\u20103\u2010epi\u2010D<jats:sub>3<\/jats:sub> did not raise serum calcium, while the same dose of 1\u03b1OHD<jats:sub>3<\/jats:sub> increased serum calcium by 3.39\u2009\u00b1\u20090.52 mg\/dl. Interestingly, in the same rats which received 1\u03b1OH\u20103\u2010epi\u2010D<jats:sub>3<\/jats:sub> we also noted a reduction in circulating PTH levels by 65\u2009\u00b1\u20097%. This ability of 1\u03b1OH\u20103\u2010epi\u2010D<jats:sub>3<\/jats:sub> to suppress PTH levels in normal rats without altering serum calcium was further tested in rats with reduced renal function. The results indicated that the ED50 of 1\u03b1OH\u20103\u2010epi\u2010D<jats:sub>3<\/jats:sub> for suppression of PTH was only slightly higher than that of 1\u03b1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub>, but that the threshold dose of the development of hypercalcemia (total serum Ca &gt;\u200910.5 mg\/dl) was nearly 80 times higher. These findings indicate that 1\u03b1OH\u20103\u2010epi\u2010D<jats:sub>3<\/jats:sub> is a highly selective vitamin D analog with tremendous potential for treatment of secondary hyperparathyroidism in chronic renal failure patients. \u00a9 2005 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcb.20553","type":"journal-article","created":{"date-parts":[[2005,8,8]],"date-time":"2005-08-08T22:28:09Z","timestamp":1123540089000},"page":"569-578","source":"Crossref","is-referenced-by-count":44,"title":["Isolation and identification of 1\u03b1\u2010hydroxy\u20103\u2010epi\u2010vitamin D<sub>3<\/sub>, a potent suppressor of parathyroid hormone secretion"],"prefix":"10.1002","volume":"96","author":[{"given":"Alex J.","family":"Brown","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cynthia S.","family":"Ritter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.S.","family":"Weiskopf","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"Vouros","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gino J.","family":"Sasso","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milan R.","family":"Uskokovic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guochun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G. Satyanarayana","family":"Reddy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,8,8]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0303-7207(00)00330-0"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1006\/excr.1998.4044"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.2174\/1381612003400416"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4644(19990401)73:1<106::AID-JCB12>3.0.CO;2-Q"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.1999.00386.x"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/17.suppl_10.41"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.3177\/jnsv.47.108"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M311473200"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.23.133"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0401656101"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00430a051"},{"key":"e_1_2_6_13_1","first-page":"172","volume-title":"Vitamin D: A pluripotent steroid hormone: Structural studies, molecular endocrinology and clinical applications","author":"Reddy GS","year":"1994"},{"key":"e_1_2_6_14_1","first-page":"139","volume-title":"Vitamin D, chemistry, biology, and clinical applications of the steroid hormone","author":"Reddy GS","year":"1997"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1006\/abbi.2000.2074"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0039-128X(00)00228-2"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.2002.17.12.2206"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(99)00377-4"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S8756-3282(99)00019-8"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/0272-6386(95)90455-7"}],"container-title":["Journal of Cellular Biochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcb.20553","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcb.20553","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,8]],"date-time":"2023-10-08T19:15:39Z","timestamp":1696792539000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcb.20553"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,8,8]]},"references-count":19,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2005,10,15]]}},"alternative-id":["10.1002\/jcb.20553"],"URL":"https:\/\/doi.org\/10.1002\/jcb.20553","archive":["Portico"],"relation":{},"ISSN":["0730-2312","1097-4644"],"issn-type":[{"value":"0730-2312","type":"print"},{"value":"1097-4644","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,8,8]]}}}